142 replies to this topic

[farware]

I just want to sum up a few things for myself and maybe others who are trying to figure this out. I'm 29, suffering from an inability to focus on tasks I don't like and often misplace things. Have some social issues and some OCD, but its managable nothing too serious. My genetic profile says I can develop both ADHD and schizophrenia. One parent is suffering from Schizophrenia but I personally feel like I have low dopamine, not high dopamine, for example when I drink coffee after a long time again I can often focus very well. 

 

ADHD: 

• Low Dopamine 
• Confusion, Forgetful, Anxiety
• OCD Possible
• Impaired Attention But More Ommission Errors And Slower (ADHD-I)
• Possible Pre-cursor? Prodromal symptoms of schizophrenia may include ADHD
• Treatment: Dopamine Receptor Upregulation, Short-Term: Dopamine Releasing Meds 

 

Schizophrenia: 

• High Dopamine
• Delusions, Voices, Paranoia
• OCD Possible
• Impaired Attention Possible (Initial Focus More Difficult)
• Treatment: Dopamine Blockers, Anti-psychotics

 

http://www.sciencedi...887617707001278

 

 

Specifically interesting for ADHD-I(nattentive)

ADHD-I subjects reacted slower all along compared to ADHD 

Although not confirmed entirely, we consider the pattern that emerged here compatible with a “lethargic attention deficit”.

 

Compared to the other two groups, their reaction time became more variable as a function of time on task. As hypothesized, they committed more omission errors on the last third of the test.

 

 

____________

 

 

Possible upregulation of D2 (Dopamine) receptors through NMDA antagonist

 

• - Inositol (test on myself, confirmed to work, it also lowers anxiety and increases focus)
• - Forskolin 
• - Huperzin A  http://www.longecity...ut-huperzine-a/
• - Zinc, Taurine, Cats Claw
• - Memantine, Ketamine

 

 

Possibly beneficial for schizophrenia are then NMDA agonists that can block Dopamine

 

• - Glycine
• - D-Serine
• - Sarcosine? (not sure about NMDA agonist but may be beneficial)

 

Both glycine and d-serine (NMDA agonists) have been found to be decreased in both the blood and cerebrospinal fluid of people with schizophrenia compared to controls. This has all led to the hypothesis that people with schizophrenia have too little NMDA and that is one cause of some of the symptoms of the disease – particularly the negative symptoms and the cognitive deficits.

 

http://www.schizophr...com/glycine.htm

 

____________________________

 

 

 

I am personally trying to figure out where I fall in the spectrum. I have serious problems with low dopamine. I abused coffee for 2 years, was addicted to video games as a teenager and I am probably somewhat addicted to the internet now, however I have genes for both ADHD and Schizophrenia and they may go hand in hand according to some studies which totally irritates me because that would mean it could swing from one extreme to the other. 

 

I am also trying to figure out what is real science here and what is mumbojumbo. I know gene expression plays a great role. 

 

For example, in alternative health you will often read that most schizophrenics have pyroloruia. I just can figure out whether I should take it seriously. They'd recommend Zinc and B6 in high doses. Taking B6 / P5P in high doses would improve methylation and decrease dopamine, thats about it. Zinc can obviously improve stress-handling. Yes, I and some other members share probably 20 out of 20 symptoms on those "symptom lists" but they are also very general symptoms (like white spots on fingernails or more stretch marks - possibly due to zinc, magnesium deficiency or similar). 

 

So my conclusions thus far:

 

Talk to a doctor about a possible brain scan or if not possible write a very extensive list of symptoms to exclude the possibility of schizophrenia. Then if I have in fact ADHD upregulate Dopamine receptors with Inositol and improve Dopamine production with Ginko. Both seems to work fine for me already. Also went on T3 meds (thyroid meds) which immediately relived a lot of symptoms including constipation. My body apparently is unable to convert T4 into T3. I also seem very high in homocysteine, which is why I will start TMG again. I am taking pregnenolone to balance my hormones and it seems to work to some extent (cant rule out placebo but its doing something).

 

Would be great to get some feedback here. Did I get anything wrong, please correct me and I'll fix it. 

 

Moderator's corrections in red.

Edited by YOLF, 29 June 2016 - 10:03 AM.

[farware]

One thing I would like to add after reading through the forums. Many people here take way too many things at once without thinking about their "stacks"

Some people are actually taking Tianeptine and Selegiline at the same time in a "stack". I don't call that a stack, it's a horrible idea to mix a MAO-B inhibitor with a Dopamine agonist. The result is obvious, they come here and complain about those drugs as inefficient. 

 

A MAO-B inhibitor will obviously interact with the Dopamine agonist and you will have a long turnover rate, meaning too much dopamine in your brain. This could induce psychosis and is not recommended in people prone to schizophrenia, bipolar and all that good stuff. 

 

In my opinion its better to try one thing at a time and then you can build a stack after writing down the effects. Right?

 

--

 

I have ordered some Tianeptine but I will first try to upregulate my receptors naturally. I think a lot of people simply have problems with sulfate pathways or whatever and thats why they have problems with their NT turnover rates and stuff due to low enzyme activity. 

 

So yea, that are just some of my observations but of course I can be wrong. 

Edited by farware, 12 June 2016 - 03:33 PM.

[gamesguru]

the nmda blockers can be useful in their own rite, because glutamatergic dysfunction plays a role too. the problem youll realize with more research, is that different regions have hypo or hyper NT states. iirc, the frontal lobes has too much glutamate and the stratium not enough, and the opposite relationship with dopamine.

 

these opposite expressions of DA/Glu roughly mediate the negative/cognitive and positive symptoms (youll have to check which does which). you cant really tell two different medicines to just go to two different brain regions. theyre going to overlap, and you just have to decide on one, probably nmda blockers and d2 agonists.

Abnormal Striatal Dopamine Transmission in Schizophrenia
Jerome Brunelin,*,1,2,3 Shirley Fecteau,3,4 and Marie-Françoise Suaud-Chagny (2013)

Despite numerous revisions and reformulations, dopamine (DA) hypothesis of schizophrenia remains a pivotal neurochemical hypothesis of this illness. The aim of this review is to expose and discuss findings from positron emission tomography (PET) or single-photon-emission computed tomography (SPECT) studies investigating DA function in the striatum of medicated, drug-naïve or drug-free patients with schizophrenia and in individuals at risk compared with healthy volunteers.

DA function was studied at several levels: i) at a presynaptic level where neuroimaging studies investigating DOPA uptake capacity clearly show an increase of [striatal] DA synthesis in patients with schizophrenia; ii) at a synaptic level where neuroimaging studies investigating dopamine transporter availability (DAT) does not bring any evidence of dysfunction; iii) and finally, neuroimaging studies investigating DA receptor density show a mild increase of D2 receptor density in basic condition and, an hyperreactivity of DA system in dynamic condition.

These results are discussed regarding laterality, sub-regions of striatum and implications for the at-risk population. Striatal DA abnormalities are now clearly demonstrated in patients with schizophrenia and at risk population and could constitute an endophenotype of schizophrenia. Subtle sub-clinical striatal DA abnormalities in at risk population could be a biomarker of transition from a vulnerability state to the expression of frank psychosis.

 

Hypodopaminergic and hypernoradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder--the spontaneously hypertensive rat.
Russell VA1. (2002)

Evidence supports dysfunction of dopaminergic and noradrenergic systems in patients with attention-deficit hyperactivity disorder (ADHD). Noradrenergic and dopaminergic systems exert distinct modulatory actions on the transfer of information through neural circuits that connect functionally distinct cortical areas with separate striatal regions and remain segregated in parallel striato-pallidal-thalamic and striato-substantia nigra pars reticulata-thalamic pathways. Prefrontal cortex performance is maximal at moderate stimulation of postsynaptic dopaminergic and noradrenergic receptors, and is reduced by either higher or lower levels of receptor stimulation. Spontaneously hypertensive rats (SHR) are generally considered to be a suitable genetic model for ADHD, since they display hyperactivity, impulsivity, poor stability of performance, impaired ability to withhold responses and poorly sustained attention, when compared with their normotensive Wistar-Kyoto (WKY) control rats. Evidence suggests that terminals of mesocortical, mesolimbic and nigrostriatal dopaminergic neurons of SHR release less dopamine in response to electrical stimulation and/or depolarization as a result of exposure to high extracellular K+ concentrations, than WKY. Vesicular storage of dopamine was suggested to be impaired in SHR, causing leakage of dopamine into the cytoplasm and increased d-amphetamine-induced transporter-mediated release. While electrically stimulated release of dopamine appears to be decreased in prefrontal cortex of SHR suggesting hypodopaminergic function, autoreceptor-mediated inhibition of norepinephrine release appears to be impaired in SHR, suggesting that noradrenergic function may be poorly regulated in the prefrontal cortex of the SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between noradrenergic and dopaminergic systems in the prefrontal cortex, with inhibitory dopaminergic activity being decreased and noradrenergic activity increased relative to controls.

Elevated Prefrontal Cortex γ-Aminobutyric Acid and Glutamate-Glutamine Levels in Schizophrenia Measured In Vivo With Proton Magnetic Resonance Spectroscopy FREE
Lawrence S. Kegeles, MD, PhD; Xiangling Mao, MS; Arielle D. Stanford, MD; Ragy Girgis, MD; Najate Ojeil, MA; Xiaoyan Xu, PhD; (2012)

Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains.
Noga JT1, Hyde TM, Herman MM, Spurney CF, Bigelow LB, Weinberger DR, Kleinman JE. (1997)

INTRODUCTION:
Previous postmortem studies of glutamate receptors and uptake sites have shown decreased D-aspartate (D-Asp) (a marker for the high affinity glutamate uptake site) and elevated (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK-801) binding in the putamen in schizophrenia and elevated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor binding in the caudate nucleus of schizophrenics who committed suicide. The relative effects of schizophrenia, suicide, and neuroleptic treatment in these findings is unclear. This study further explores binding to glutamate receptors (NMDA, kainic acid, and AMPA) and uptake sites in postmortem striatal structures in schizophrenics relative to three control groups (normal controls, neuroleptic-treated controls, and nonpsychotic suicides).
METHODS:
We compared the binding densities of tritium-labeled ligands 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), kainic acid (KA), MK-801, and D-Asp, which target the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), KA, and N-methyl-D-aspartic acid (NMDA) ionotropic receptor sites and the glutamate uptake site, respectively, in postmortem striatal/accumbens tissue from six DSM-III-R schizophrenics, eight normal controls, eight neuroleptic-treated controls, and eight suicide victims using standard receptor autoradiographic methods.
RESULTS:
Binding of [3H] CNQX (AMPA receptors) was significantly different among the four groups across the subdivisions of the striatum: caudate, putamen, and nucleus accumbens (ANOVA P = .0007, .002, and .004, respectively). The schizophrenia group had higher mean CNQX binding in the caudate nucleus than normal (P = .005) and neuroleptic controls (P = .006) but not suicides (P = .6), who were also higher than normals and neuroleptic-treated controls (P = .05). The binding densities of tritiated MK-801, KA, and D-Asp were not significantly different among the four groups of subjects in any of the striatal regions examined.
CONCLUSIONS:
The data suggest there may be an increased density of AMPA receptor sites in the caudate nucleus in schizophrenia that is not apparently due to neuroleptic treatment. A similar increase was also seen the suicide group. Although these data do not confirm previous reports of an increase in [3H]MK-801 or a decrease in [3H]D-Asp binding in the basal ganglia in schizophrenia, the increased caudate AMPA binding observed here could reflect decreased cortical glutamatergic innervation of the caudate. Its implication for suicide is unclear.

Transient and Selective Overexpression of Dopamine D2 Receptors in the Striatum Causes Persistent Abnormalities in Prefrontal Cortex Functioning
Christoph Kellendonk6, Eleanor H. Simpson6,correspondenceemail, H. Jonathan Polan, Gaël Malleret (2006)

 

Glutamate and dopamine components in schizophrenia
Philip Seeman (2009)

The treatment of schizophrenia for the last half century has been with dopamine (DA) D2 receptor blockers, implicating a hyperdopamine basis for psychosis. However, a 2007 report found that the glutamate agonist LY404039 was effective in schizophrenia, suggesting a hypoglutamate state for the illness. Although phencyclidine psychosis also supports a hypoglutamate cause, assessing the basic and clinical findings shows that phencyclidine has DA D2 agonist actions as well. Accurate Dreiding models of phencyclidine and the LY glutamate agonists precisely fit the known tetrahedral model of the D2 receptor that accommodates all DA agonists. A further view is that metabotropic glutamate agonists also exert D2 agonism, and their antipsychotic doses (about 100 mg/d) are predicted by their dissociation constants (about 20 nM) for D2. Hence, the clinical antipsychotic action of a glutamate agonist may depend on its ability to interfere with DA neurotransmission by its DA partial agonism.

 

The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common Pathway
Oliver D. Howes2,3 and Shitij Kapur (2009)

The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia—version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.

 

[farware]

That's very interesting

 

However, a 2007 report found that the glutamate agonist LY404039 was effective in schizophrenia, suggesting a hypoglutamate state for the illness.

 

Some researchers are proposing that Schizophrenics have hypofunctioning glutamate receptors whereas ADHD-I patients have probably hyperfunctioning glutamate receptors. ADHD can be a prodromal symptom so I guess that this can flip from one extreme to the other due to external factors e.g. illness, stress, infection?

 

But as you pointed out, different regions in the brain are in this hypo/hyper state and that's why its so difficult to treat, because you will always have some overlap and finding a balance is difficult. So new meds would have to target a specific brain region and lower or increase glutamate only for that brain region if that is even possible. 

 

Then on top you have the dopamine and GABA and other NTs interfering, probably Acetylcholine is also somehow implicated I'd assume. 

 

__

 

What I concluded so far is that the best meds do neither increase or decrease NTs but modulate the pathways and improve receptor density and sensitivty. 

 

 

 

 

 

the nmda blockers can be useful in their own rite, because glutamatergic dysfunction plays a role too. the problem youll realize with more research, is that different regions have hypo or hyper NT states. iirc, the frontal lobes has too much glutamate and the stratium not enough, and the opposite relationship with dopamine.

 

these opposite expressions of DA/Glu roughly mediate the negative/cognitive and positive symptoms (youll have to check which does which). you cant really tell two different medicines to just go to two different brain regions. theyre going to overlap, and you just have to decide on one, probably nmda blockers and d2 agonists.

 

Edited by farware, 24 June 2016 - 06:09 PM.

[psychejunkie]

this is SOOO wrong to categorize these complex disorders into High vs Low of something!!!

 

Please STOP reading low-science webpages about what/why/howtos of brain power, mind boosters, etc junk shits and get a valid book and start reading science, people!!!

 

such a wrongful statements might result in dangerous conclusions, and eventually somebody may hurt him/herself by erratically changing their neurotransmitters levels..

I am not an old member here, but I have seen a lot of topics/posts like this by irresponsible and low educated people.

 

Fundamentals of Neural Science, 5th Ed by Eric R. Kandel et al is a very good book to start with.

[gamesguru]

wrong to categorize these complex disorders into High vs Low of something!!!

Fundamentals of Neural Science, 5th Ed by Eric R. Kandel et al is a very good book to start with.

 

right, we're breaking it down into high in region xyz but low in region abc. pretty specific.

also i have that book in my basement, it makes a fantastic dust collector and dumbbell.

[Mind_Paralysis]

I made some research into Kynurenic Acid regarding ADHD previously, and my assessment was similar to yours, that the two disorders seems to almost exist in negation to each other.

 

Prime one being KYNA-levels - altered L-tryptophan activity have been recorded in ADHD - L-tryptophan is later converted into Serotonin, Melatonin and Kynurenic Acid. Slightly lower KYNA-levels have been reported in ADHD, while ultra-high levels have been seen in Schizo - hence why some believe the Kyna-hypothesis of schizo is now the leading one - since it fuses the dopaminergic and glutamatergic theories into one.

 

Read more about my research here:

http://www.longecity...c-acid-in-adhd/

 

Now... you're a tricky case... because you've got BOTH in your family, but is primarily showing ADHD-PI symptoms at the moment.

 

What I would suggest is either to wait with treatment until you have passed the age of most likely break-out of schizo symptoms - as I understand it, that is between the age of 16-30. I would also suggest you get a DNA-test through 23andme.com, and then run it through another service called Promethease.

 

That should reveal if you carry the DRD4-Vntr-7+ (seven and longer at the end impairs attention) variation of the Dopamine receptor subtype 4 gene. If you have it, then it's most likely going to cause inattention (it's one of the candidate-genes for ADHD, but a recent study found it to be more associated with inattention than hyperactivity) - I have it, and I suspect it's a big part of my ADHD-PI (or SCT it would seem) pathology.

 

If so, then check out the ultra-selective D4-agonist called A-412,997, it doesn't just help with attention, but it has also been found to be effective at treating the negative symptoms of Schizophrenia without triggering Manic or psychotic episodes! So, if you do have both Schizo and ADHD, then it's the only stimulant other than Modafinil that I can find which won't trigger psychosis.

 

Only caveat is of course that it's super-rare and ultra-expensive and I have yet to find a single person alive who has ever tried it...

[farware]

 

 

What I would suggest is either to wait with treatment until you have passed the age of most likely break-out of schizo symptoms - as I understand it, that is between the age of 16-30. I would also suggest you get a DNA-test through 23andme.com, and then run it through another service called Promethease.

 

That should reveal if you carry the DRD4-Vntr-7+ (seven and longer at the end impairs attention) variation of the Dopamine receptor subtype 4 gene. If you have it, then it's most likely going to cause inattention (it's one of the candidate-genes for ADHD, but a recent study found it to be more associated with inattention than hyperactivity) - I have it, and I suspect it's a big part of my ADHD-PI (or SCT it would seem) pathology.

 

I actually have already done that. I'm rs1800955(C;T) and rs11246226(A;A)

 

It states: variant in the promoter region upstream of the DRD4 gene on chromosome 11 

 

I couldnt figure out whether I carry the DRD4-Vntr-7+ yet, where exactly would I find that?

 

The DRD4 variation is causing 1) increased susceptibility to novelty seeking 2) increased risk of schizophrenia in limited study 

[farware]

this is SOOO wrong to categorize these complex disorders into High vs Low of something!!!

 

Please STOP reading low-science webpages about what/why/howtos of brain power, mind boosters, etc junk shits and get a valid book and start reading science, people!!!

 

such a wrongful statements might result in dangerous conclusions, and eventually somebody may hurt him/herself by erratically changing their neurotransmitters levels..

I am not an old member here, but I have seen a lot of topics/posts like this by irresponsible and low educated people.

 

Fundamentals of Neural Science, 5th Ed by Eric R. Kandel et al is a very good book to start with.

 

We are already discussing that in this thread that its in various parts of the brain that are currently difficult to reach for medications, doesn't change the fact that this is what is happening inside the brain. Most often the PFC is involved as well so of course you cant generalize and say that schizo is caused by too much dopamine but its important to know that there are distinct differences between ADHD and Schizophrenia and how certain medications such as Ritalin could potentially induce psychosis because it is increasing dopamine too much and affecting glutamate receptors. 

[Mind_Paralysis]

 

 

 

What I would suggest is either to wait with treatment until you have passed the age of most likely break-out of schizo symptoms - as I understand it, that is between the age of 16-30. I would also suggest you get a DNA-test through 23andme.com, and then run it through another service called Promethease.

 

That should reveal if you carry the DRD4-Vntr-7+ (seven and longer at the end impairs attention) variation of the Dopamine receptor subtype 4 gene. If you have it, then it's most likely going to cause inattention (it's one of the candidate-genes for ADHD, but a recent study found it to be more associated with inattention than hyperactivity) - I have it, and I suspect it's a big part of my ADHD-PI (or SCT it would seem) pathology.

 

I actually have already done that. I'm rs1800955(C;T) and rs11246226(A;A)

 

It states: variant in the promoter region upstream of the DRD4 gene on chromosome 11 

 

I couldnt figure out whether I carry the DRD4-Vntr-7+ yet, where exactly would I find that?

 

The DRD4 variation is causing 1) increased susceptibility to novelty seeking 2) increased risk of schizophrenia in limited study 

 

 

Right, I have the rs11246226(A;C) variant, and I have no history of schizophrenia in any part of my family. Hmm...! Well, you do - and you happen to be (A;A). There's only one single study, with low quality of evidence for the effect though, so it may not mean too much in the long run.

 

I have the rs1800955(C;T) version of that gene, and I do have ADHD with symptoms that are similar to yours.

 

If we are going to go by SNPedia's chart, then rs1800955(C;T) has a maximum magnitude of 2,1, and  rs11246226(A;A) has a maximum magnitude of 1,2. I'm not entirely sure, but I think the magnitude implies most likely effect of this gene on a certain property of your body or personality. I read that as the first CT is more likely to give you ADHD than the second AA is to give you schizophrenia.

 

https://www.snpedia.com/index.php/DRD4

 

Regarding how to figure out which vntr you have... damn hard! I just assumed I had a long variant, since I have one which implies increased susceptibility to novelty seeking - and that was supposed to be the vntr-7 and upwards. The way I've understood it until now, the 7 number is a measure of the tail end of the molecular composition of this gene, apparently the longer this number is, the more faulty your receptor will become, because the longer compositions are apparently repeats in the molecular structure, which are pointless to function, and actually makes for less correctly formed D4-receptors - it's a bunch of extra junk, and it just gets in the way.

 

This website supposedly let's you use your raw data to check this stuff right in your Firefox-browser...

 

http://www.eupedia.c...raits_snp.shtml

 

Buut... I just realized that SNP's are not the same as VNTR's, so I'm guessing you CAN'T actually see this, with your 23andme.com data! >_<

 

Apparently Familytree-DNA does do VNTR-testing, but they don't give you any interpretation, so you'd have to either plug their test-data into another service, or do some deep digging in it.

 

http://forums.family...ead.php?t=30469

 

I apologize to everyone I have misled by mentioning 23andme and getting VNTR-data... it was a GRAVE mistake. My word... I feel awful!

Edited by Stinkorninjor, 27 June 2016 - 04:02 PM.

[farware]

I think it is safe to say that messing with NTs is not what you want to do, rather modulating and balancing glutmate / dopamine receports and making sure sulfate pathways are working properly. Schizo/ADHD both seem to go hand in hand with some other gene defects. Personally I also have gene defects that cause high homocysteine (need to take folate, not folic acid!). 

 

Mainsteam medicine is at least 10 years behind all of this research that people like us are doing on a daily basis. Sometimes when I talk to a doctor I feel like talking to a 5 year old, it's so funny when you know so much more than your doc who apparently studied this. Too bad that politicis and finance basically control the industry anyway, else they wouldnt still be prescribing SSRIs after 20 years of research that they are basically useless. 

 

 

 

 

 

 

Edited by farware, 27 June 2016 - 06:07 PM.

[Mind_Paralysis]

A-412997 is very different from other compounds though, it doesn't have any of the common sideeffects from stimulants, and it doesn't trigger mania or psychosis - it's the real deal, something selective but effective enough to do the job.

 

I suppose I forgot to mention this, but the usual side-effects from D-agonists are not present with D4-selective drugs - no sexual behaviour, no gambling, no anxiety, no hyperactivity, no addiction, et c. Well.. it causes massive and PAINFUL boners, apparently! But, if you're a woman, then who cares?

 

The D4-receptor is also unique in that it's HIGHLY resistant to up or down-regulation! : O That's why it's so hard to increase attention with supplementation, or, why this drug doesn't down-regulate your D4-receptors - there's hardly any tolerance, dude. The dose you need, is the dose you need.

 

But yeah, otherwise I suppose you're right... I'm looking into Metadoxine and Pyritinole right now, and they do pretty much what you said.

[farware]

Pyritinole sounds interesting but would require a lot more research. 

 

I actually found a study that says Piracetam is modulating glutamate receptors. I believe this could be great for ADHD and Schizophrenia (for the cognitive issues anyway).  Looks like I will try that first because it seems to have a lot less side effects than Tianeptine. Tianeptine can be addictive, probably not at therapeutic doses but your probably need like 50mg of it per day for it to be effective and thats already getting close to where it could become addictive. 

 

 

Piracetam, a member of the nootropic class of drugs and a positive modulator of glutamate receptor, may be of therapeutic benefit in treating schizophrenic patients in combination with typical neuroleptics. However, a larger study to confirm our results is warranted

 

http://www.ncbi.nlm....pubmed/10583700

 

 

EDIT: Looks like we have a thread that says Piracetam may help with ADHD-PI http://www.longecity...am-for-adhd-pi/

 

 

So, for now I will stick to P5P and PEA precursors which is awesome for dream recall and neuroplasticity. I'm finally capable of doing new things again. My ADHD / depression was so severe that I was a couch-potato for a long time. Took a lot of effort to get over it. So I'm hopeful Piracetam will give me that mental edge that I need to make the next moves. I'm also slowly re-introducing Glycine. 

 

My stack right now: 

 

• Inositol 500mg x2 
• T3 
• Ginko
• Pregnenolone
• D3
• Iron
• P5P 100mg mixed with 500mg Vit C
• Raw Cacao 100%  

 

This is doing the job for now but I still cant focus as well as I'd like to, especially on activities I dont like. So Piracetam then depending on how it goes, Piracetam + Glycine but I first need to read some studies on how Glycine interacts with NDMA receptors 

 

N-methyl-D-aspartate (NMDA) receptors are the only neurotransmitter receptors whose activation requires two distinct agonists.

http://jgp.rupress.o.../145/6/513.full

 

 

So from the first look its possible the receptors would need glycine but I need to read more about it. If anyone could explain to me the glutamate-glycine connection that would be great. 

 

 

 

 

 

 

 

Edited by farware, 27 June 2016 - 11:30 PM.

[jack black]

 

I actually have already done that. I'm rs1800955(C;T) and rs11246226(A;A)

 

It states: variant in the promoter region upstream of the DRD4 gene on chromosome 11 

 

I couldnt figure out whether I carry the DRD4-Vntr-7+ yet, where exactly would I find that?

 

The DRD4 variation is causing 1) increased susceptibility to novelty seeking 2) increased risk of schizophrenia in limited study 

 

 

I have the same results. They are not particarly rare as far as I can determine. Yes, I do consider myself as having ADHD, but no history of schizophrenia in my family (yet). There is some history of borderline personality in my family. Interestingly, there is good evidence that multiple different psychiatric diseases and personality disorders are linked to the genetic polymorphism of sodium channels. Not surprizingly as drugs modulating sodium channel work well for a number of diverse psychiatric diseases and personality disorders.

 

Moreover, there is this long winded article that argues that some of those genetic "liabilities" can be actually assets in some circumstances: http://www.theatlant...success/307761/

[farware]

 

 

I actually have already done that. I'm rs1800955(C;T) and rs11246226(A;A)

 

It states: variant in the promoter region upstream of the DRD4 gene on chromosome 11 

 

I couldnt figure out whether I carry the DRD4-Vntr-7+ yet, where exactly would I find that?

 

The DRD4 variation is causing 1) increased susceptibility to novelty seeking 2) increased risk of schizophrenia in limited study 

 

 

I have the same results. They are not particarly rare as far as I can determine. Yes, I do consider myself as having ADHD, but no history of schizophrenia in my family (yet). There is some history of borderline personality in my family. Interestingly, there is good evidence that multiple different psychiatric diseases and personality disorders are linked to the genetic polymorphism of sodium channels. Not surprizingly as drugs modulating sodium channel work well for a number of diverse psychiatric diseases and personality disorders.

 

Moreover, there is this long winded article that argues that some of those genetic "liabilities" can be actually assets in some circumstances: http://www.theatlant...success/307761/

 

 

I agree that gene expression plays a great role. Unfortunately most of us go through difficult lives and will encounter at the very least one very stressful or traumatic event. Its unavoidable in todays society. So even people with great childhoods and caring parents can still end up getting depressed and for good reason. I dont consider these traits assets if they have such a profound impact one someone's central nervous system, thyroid health and general well being. 

[YOLF]

Interesting topic with some possible implications for age reversal. So here's a drive by...

 

If schizophrenia comes with an impaired production of glycine, perhaps AGE blockers (P5P, Benfotiamine, etc.... not really sure which would be most effective for preventing bad lysine conjugates) will help restore normal glycine production? Lysine's less friendly conjugates are known to burden the kidneys... perhaps drinking extra water and taking tocotrienols will keep them functioning better?

 

AGE breakers could also be useful for schizo patients potentially as damage from compromised lysine metabolism.

 

Unless of course the glycine is being used up more by the condition...

 

 

[YOLF]

 

 

 

 

What I would suggest is either to wait with treatment until you have passed the age of most likely break-out of schizo symptoms - as I understand it, that is between the age of 16-30. I would also suggest you get a DNA-test through 23andme.com, and then run it through another service called Promethease.

 

That should reveal if you carry the DRD4-Vntr-7+ (seven and longer at the end impairs attention) variation of the Dopamine receptor subtype 4 gene. If you have it, then it's most likely going to cause inattention (it's one of the candidate-genes for ADHD, but a recent study found it to be more associated with inattention than hyperactivity) - I have it, and I suspect it's a big part of my ADHD-PI (or SCT it would seem) pathology.

 

I actually have already done that. I'm rs1800955(C;T) and rs11246226(A;A)

 

It states: variant in the promoter region upstream of the DRD4 gene on chromosome 11 

 

I couldnt figure out whether I carry the DRD4-Vntr-7+ yet, where exactly would I find that?

 

The DRD4 variation is causing 1) increased susceptibility to novelty seeking 2) increased risk of schizophrenia in limited study 

 

 

Right, I have the rs11246226(A;C) variant, and I have no history of schizophrenia in any part of my family. Hmm...! Well, you do - and you happen to be (A;A). There's only one single study, with low quality of evidence for the effect though, so it may not mean too much in the long run.

 

I have the rs1800955(C;T) version of that gene, and I do have ADHD with symptoms that are similar to yours.

 

If we are going to go by SNPedia's chart, then rs1800955(C;T) has a maximum magnitude of 2,1, and  rs11246226(A;A) has a maximum magnitude of 1,2. I'm not entirely sure, but I think the magnitude implies most likely effect of this gene on a certain property of your body or personality. I read that as the first CT is more likely to give you ADHD than the second AA is to give you schizophrenia.

 

https://www.snpedia.com/index.php/DRD4

 

Regarding how to figure out which vntr you have... damn hard! I just assumed I had a long variant, since I have one which implies increased susceptibility to novelty seeking - and that was supposed to be the vntr-7 and upwards. The way I've understood it until now, the 7 number is a measure of the tail end of the molecular composition of this gene, apparently the longer this number is, the more faulty your receptor will become, because the longer compositions are apparently repeats in the molecular structure, which are pointless to function, and actually makes for less correctly formed D4-receptors - it's a bunch of extra junk, and it just gets in the way.

 

This website supposedly let's you use your raw data to check this stuff right in your Firefox-browser...

 

http://www.eupedia.c...raits_snp.shtml

 

Buut... I just realized that SNP's are not the same as VNTR's, so I'm guessing you CAN'T actually see this, with your 23andme.com data! >_<

 

Apparently Familytree-DNA does do VNTR-testing, but they don't give you any interpretation, so you'd have to either plug their test-data into another service, or do some deep digging in it.

 

http://forums.family...ead.php?t=30469

 

I apologize to everyone I have misled by mentioning 23andme and getting VNTR-data... it was a GRAVE mistake. My word... I feel awful!

 

 

I have to disagree with Rs1800955 CT being part of ADHD... Novelty seeking is about finding interest in this that and the other thing and being inspired to think about it or something else relevant to whatever enlightenment is gained... It's not the same as zoning out. It also correlates with higher IQ and visual intelligence. Though I suppose that seeking and finding novelty are two different things... still some pattern of success must exist for one to find seeking worthwhile.

[farware]

Interesting topic with some possible implications for age reversal. So here's a drive by...

 

If schizophrenia comes with an impaired production of glycine, perhaps AGE blockers (P5P, Benfotiamine, etc.... not really sure which would be most effective for preventing bad lysine conjugates) will help restore normal glycine production? Lysine's less friendly conjugates are known to burden the kidneys... perhaps drinking extra water and taking tocotrienols will keep them functioning better?

 

AGE breakers could also be useful for schizo patients potentially as damage from compromised lysine metabolism.

 

Unless of course the glycine is being used up more by the condition...

 

That's interesting that you mention Lysine. I've been taking Lysine for some time as I react very well to it, but I took it for the central nervous system not with the intention to boost glycine, will have to look into that. 

 

Thank you for your corrections, much appreciated.

 

Also, P5P is part of my stack and I am doing more research in that area right now. B vitamins seems to be implicated in depression, ADHD and lots of other issues. They found less inositol in the brains of depressed people (postmortem). What obviously makes it so complicated is that so many things are implicated, not just the one.  

 

As for age reversal, I found NAD+ of interest. 

[farware]

I have to disagree with Rs1800955 CT being part of ADHD... Novelty seeking is about finding interest in this that and the other thing and being inspired to think about it or something else relevant to whatever enlightenment is gained... It's not the same as zoning out. It also correlates with higher IQ and visual intelligence. Though I suppose that seeking and finding novelty are two different things... still some pattern of success must exist for one to find seeking worthwhile.

 

 

I always interpreted it differently. Novelty-seeking refers to less efficient Serotonin processing. It also implies that your attention is shifting a lot as you get bored easily by things. This describes me very well. I have more interests than any other person in my circle. While this is great because I have lot of insight into different things it also makes me a complete generalist and less of a specialist. I think a lot of ADHD patients could relate to that.

Edited by farware, 29 June 2016 - 10:24 AM.

[YOLF]

 

this is SOOO wrong to categorize these complex disorders into High vs Low of something!!!

 

Please STOP reading low-science webpages about what/why/howtos of brain power, mind boosters, etc junk shits and get a valid book and start reading science, people!!!

 

such a wrongful statements might result in dangerous conclusions, and eventually somebody may hurt him/herself by erratically changing their neurotransmitters levels..

I am not an old member here, but I have seen a lot of topics/posts like this by irresponsible and low educated people.

 

Fundamentals of Neural Science, 5th Ed by Eric R. Kandel et al is a very good book to start with.

 

We are already discussing that in this thread that its in various parts of the brain that are currently difficult to reach for medications, doesn't change the fact that this is what is happening inside the brain. Most often the PFC is involved as well so of course you cant generalize and say that schizo is caused by too much dopamine but its important to know that there are distinct differences between ADHD and Schizophrenia and how certain medications such as Ritalin could potentially induce psychosis because it is increasing dopamine too much and affecting glutamate receptors. 

 

 

Just curios, but how much physical activity are you getting? The pregnenolone will give you better benefits if you're working out alot and a good workout, or fitness in general will get your brain straightened out and have all the right receptors in all the right areas. I can take supplements to improve how I feel and my attitude towards things, but I think working out AND taking supplements is better than either alone, though the spectrum of benefits from either is unique.

[YOLF]

 

Interesting topic with some possible implications for age reversal. So here's a drive by...

 

If schizophrenia comes with an impaired production of glycine, perhaps AGE blockers (P5P, Benfotiamine, etc.... not really sure which would be most effective for preventing bad lysine conjugates) will help restore normal glycine production? Lysine's less friendly conjugates are known to burden the kidneys... perhaps drinking extra water and taking tocotrienols will keep them functioning better?

 

AGE breakers could also be useful for schizo patients potentially as damage from compromised lysine metabolism.

 

Unless of course the glycine is being used up more by the condition...

 

That's interesting that you mention Lysine. I've been taking Lysine for some time as I react very well to it, but I took it for the central nervous system not with the intention to boost glycine, will have to look into that. 

 

Thank you for your corrections, much appreciated.

 

Also, P5P is part of my stack and I am doing more research in that area right now. B vitamins seems to be implicated in depression, ADHD and lots of other issues. They found less inositol in the brains of depressed people (postmortem). What obviously makes it so complicated is that so many things are implicated, not just the one.  

 

As for age reversal, I found NAD+ of interest. 

 

The studies generally use these things to indicate other larger understanding. You need to understand more of the chemistry involved. Niner and Maxwatt are awesome at this. The greater your command of the hard science behind everything, the better your understanding of the studies. Everything will make more sense. I know I'm always tempted to read another study on this or that for faster gratification and low hanging science fruits... but it really is worth the hard work to get the hard science/chemistry background. The implications lead you to the more important details.

[psychejunkie]

 

this is SOOO wrong to categorize these complex disorders into High vs Low of something!!!

 

Please STOP reading low-science webpages about what/why/howtos of brain power, mind boosters, etc junk shits and get a valid book and start reading science, people!!!

 

such a wrongful statements might result in dangerous conclusions, and eventually somebody may hurt him/herself by erratically changing their neurotransmitters levels..

I am not an old member here, but I have seen a lot of topics/posts like this by irresponsible and low educated people.

 

Fundamentals of Neural Science, 5th Ed by Eric R. Kandel et al is a very good book to start with.

 

We are already discussing that in this thread that its in various parts of the brain that are currently difficult to reach for medications, doesn't change the fact that this is what is happening inside the brain. Most often the PFC is involved as well so of course you cant generalize and say that schizo is caused by too much dopamine but its important to know that there are distinct differences between ADHD and Schizophrenia and how certain medications such as Ritalin could potentially induce psychosis because it is increasing dopamine too much and affecting glutamate receptors. 

 

 

Even discussing specific neurotransmitters' level in different brain region isn't very accurate and cant explain such diseases. there are several receptors, protein and gene regulations, synapse and dendrite spines activities, etc..... involved that discussing a complex disease like Schizophrenia in Low/high level of something in PFC or elsewhere makes me laugh. 

although, this thread have came to interesting information and I hope I'd learn more from you guys, thanks anyway.

[YOLF]

 

I have to disagree with Rs1800955 CT being part of ADHD... Novelty seeking is about finding interest in this that and the other thing and being inspired to think about it or something else relevant to whatever enlightenment is gained... It's not the same as zoning out. It also correlates with higher IQ and visual intelligence. Though I suppose that seeking and finding novelty are two different things... still some pattern of success must exist for one to find seeking worthwhile.

 

 

I always interpreted it differently. Novelty-seeking refers to less efficient Serotonin processing. It also implies that your attention is shifting a lot as you get bored easily by things. This describes me very well. I have more interests than any other person in my circle. While this is great because I have lot of insight into different things it also makes me a complete generalist and less of a specialist. I think a lot of ADHD patients could relate to that.

 

 

In that case, it's more of an environmental thing than a disease... Do you study enough or do you not? Generalists get paid more and make better (project) managers.  Less serotonin (or wasting it) is a good thing... the differential between sero and dopamine imo are responsible for motivation. Higher dopamine and lower serotonin make you work harder! I guess it means going all in or not making the most of yourself. So it would seem that discipline is a factor as well. Don't let people distract you or knock you off your track or you'll generalize outside of your element. Keep focused on your interests and be the boss!

Generalist and specialist are also relative terms. Don't let them define you to any serious extent, but keep an eye on the job titles.

[farware]

Just curios, but how much physical activity are you getting? The pregnenolone will give you better benefits if you're working out alot and a good workout, or fitness in general will get your brain straightened out and have all the right receptors in all the right areas. I can take supplements to improve how I feel and my attitude towards things, but I think working out AND taking supplements is better than either alone, though the spectrum of benefits from either is unique.

 

 

I work out several days a week. More and I get a sort of hangover but it has to do with another gene defect affecting red blood cells (they are rounder than in normal people)

 

 

 

 

The studies generally use these things to indicate other larger understanding. You need to understand more of the chemistry involved. Niner and Maxwatt are awesome at this. The greater your command of the hard science behind everything, the better your understanding of the studies. Everything will make more sense. I know I'm always tempted to read another study on this or that for faster gratification and low hanging science fruits... but it really is worth the hard work to get the hard science/chemistry background. The implications lead you to the more important details.

 

 

 

Yes, that's true. I will look into the authors you mentioned. Unfortunately I lack even basic chemistry knowledge, which is really annoying because it would help so much with this. Might read a few books about it 

 

 

 

Even discussing specific neurotransmitters' level in different brain region isn't very accurate and cant explain such diseases. there are several receptors, protein and gene regulations, synapse and dendrite spines activities, etc..... involved that discussing a complex disease like Schizophrenia in Low/high level of something in PFC or elsewhere makes me laugh. 

although, this thread have came to interesting information and I hope I'd learn more from you guys, thanks anyway.

 

 

I agree, there are way too many things involved which is why we still have no reliable medications for it. I often try to simplify things too much whenever I can before I dig deeper. 

 

 

 

In that case, it's more of an environmental thing than a disease... Do you study enough or do you not? Generalists get paid more and make better (project) managers.  Less serotonin (or wasting it) is a good thing... the differential between sero and dopamine imo are responsible for motivation. Higher dopamine and lower serotonin make you work harder! I guess it means going all in or not making the most of yourself. So it would seem that discipline is a factor as well. Don't let people distract you or knock you off your track or you'll generalize outside of your element. Keep focused on your interests and be the boss!

 

Generalist and specialist are also relative terms. Don't let them define you to any serious extent, but keep an eye on the job titles.

 

I'm selfemployed (internet entrepreneur) and my lack of focus basically killed my first business. I had to build up an entirely different company from the ground up because I could no longer focus on writing articles which is what I used to do for a living. Its getting better but I'm now working in area I have no experience in whatsoever (eCommerce), so I'm constantly questioning myself. It's a little annoying, probably some sort of anhedonia as well because I lost interest in most of the activities I used to enjoy which is why I am even considering trying Piracetam or TIaneptine. I just cant function like other people. Losing focus or complete inability to even start working on many days. Right now I'm sleep deprived, thats when I'm functioning best and feel a lot less stressed out, really weird but thats one of the most reliable ways to break the cycle of depression. I have a variation of the CLOCK gene too so I have an evening preference built in which is annoying because I cant keep a schedule like other people and wake up early. I think its evolutionary that those are simply gene traits from people that were out hunting. There's an interesting theory that ADHD people have more genes of early hunter-societies and thats why they dont function in todays world as well as others.

Edited by farware, 29 June 2016 - 11:22 AM.

[YOLF]

What's the blood condition called?

[farware]

What's the blood condition called?

 

It's called spherocytosis but didn't want to go too much offtopic. Basically the red blood cells have a different shape (rounder) die faster and since too much physical activity can speed up the destruction of red blood cells its not a good thing for me personally. 

 

EDIT: Its luckily only a mild form so its not affecting me that much like some others with the defect. Of course there can be interactions since red blood cells carry oxygen but my symptoms and gene profile tell a different story. Theres also not much I can do about it other than supplementing with L-Citrulline, Folate and keeping an eye on Iron levels. 

Edited by farware, 29 June 2016 - 11:43 AM.

[YOLF]

The early hunter theory is junk science... just people trying to make news articles... we all came from people who hunted stuff... Agriculture is only a few/several thousand years old... The same connections they would say come from hunters would also make people better survivors and gatherers, not to mention more advanced farmers... What they were was more independent, more self reliant, and more capable on their own. I almost just want to call them haters and move on... See, there are lots of social scientists who like to think their kind of social intelligence is so desirable that others aren't necessary and that we can stop innovating. More than anything, ADHD, or at least certain kinds is more of a maladaptation, or result of social negligence or intentional social stratifications?

[YOLF]

 

What's the blood condition called?

 

It's called spherocytosis but didn't want to go too much offtopic. Basically the red blood cells have a different shape (rounder) die faster and since too much physical activity can speed up the destruction of red blood cells its not a good thing for me personally. 

 

EDIT: Its luckily only a mild form so its not affecting me that much like some others with the defect. Of course there can be interactions since red blood cells carry oxygen but my symptoms and gene profile tell a different story. Theres also not much I can do about it other than supplementing with L-Citrulline, Folate and keeping an eye on Iron levels. 

 

Which Rs1801133 snp do you have? Any particular type of folate?

 

Any link to what's being discussed?

[farware]

Which Rs1801133 snp do you have? Any particular type of folate?

 

 

Any link to what's being discussed?

 

 

rs1801133(C;T)

1 copy of C677T allele of MTHFR = 60% efficiency in processing folic acid = could have somewhat elevated homocysteine and low B12 and folate levels

 

 

 

I am taking methylfolate since it is known that folic acid cannot be converted reliably into folate just like T4 cannot be reliably converted into T3. That's why I said modern medicine is 10 years behind current research, they still assume the conversion process always happens while there is evidence that it does not happen. 

 

I don't see a link other than high homocysteine which could be linked to depression and possible glutathione implications? I am already supplementing accordingly but it will probably take some time until the pathways are restored / balanced?

 

Edited by farware, 29 June 2016 - 12:03 PM.

[jack black]

 

 

 

I always interpreted it differently. Novelty-seeking refers to less efficient Serotonin processing. It also implies that your attention is shifting a lot as you get bored easily by things. This describes me very well. I have more interests than any other person in my circle. While this is great because I have lot of insight into different things it also makes me a complete generalist and less of a specialist. I think a lot of ADHD patients could relate to that.

 

 

Agree with you. I always felt the novelty seeking was a party of my ADHD. I also have a variety of special interests and hobbies, but I'm an ultra-specialized professional (go figure).

 

 

 

Even discussing specific neurotransmitters' level in different brain region isn't very accurate and cant explain such diseases. there are several receptors, protein and gene regulations, synapse and dendrite spines activities, etc..... involved that discussing a complex disease like Schizophrenia in Low/high level of something in PFC or elsewhere makes me laugh. 

although, this thread have came to interesting information and I hope I'd learn more from you guys, thanks anyway.

 

 

Stop being abnoxious. This forum is not a peer review disertation and it doesn't have to meet your standards. If you don't like it, don't read it. Why are you reading this in the first place? I see, you're learning new things, LOL.

 

 

I work out several days a week. More and I get a sort of hangover but it has to do with another gene defect affecting red blood cells (they are rounder than in normal people)

 

 

While it may be your anemia alright, you might want to look into low endorphins, too. That will make feel down after excercise. It's one of my life long problems. I'm even considering low dose Naltrexone. Or DLPA.

 

 

It's called spherocytosis but didn't want to go too much offtopic. Basically the red blood cells have a different shape (rounder) die faster and since too much physical activity can speed up the destruction of red blood cells its not a good thing for me personally. 

 

EDIT: Its luckily only a mild form so its not affecting me that much like some others with the defect. Of course there can be interactions since red blood cells carry oxygen but my symptoms and gene profile tell a different story. Theres also not much I can do about it other than supplementing with L-Citrulline, Folate and keeping an eye on Iron levels. 

 

 

Interesting, it's quite a rare disease. This is actually within my professional expertise. Are you of northern European ethnicity? By keeping eye on iron, you mean not too high, right?

 

Are you taking plenty of B12 with your methylfolate?